Ondetti et al. in U.S. Pat. No. 4,105,776 disclose proline derivatives having the formula ##STR4## wherein n is 0, 1 or 2;
R.sub.2 is hydrogen, acyl, etc.; PA1 R is hydroxy, NH.sub.2 or lower alkoxy; PA1 R.sub.1 and R.sub.4 each is hydrogen, lower alkyl, phenyl or phenyl-lower alkyl; PA1 R.sub.3 is hydrogen, hydroxy or lower alkyl. PA1 R.sub.3 and R.sub.4 each is hydrogen, lower alkyl or trifluoromethyl not more than one being trifluoromethyl, and at least one of R.sub.2, R.sub.2 ', PA1 R.sub.3 or R.sub.4 is a halogen or trifluoromethyl substituent represented by the named symbol as defined above; PA1 m is 1 or 2; and PA1 n is 0 or 1. PA1 R.sub.2 is hydrogen or benzoyl; and PA1 Q is a straight or branched chain alkylene with 1 to 3 carbon atoms. PA1 R is hydrogen or lower alkyl; PA1 R.sub.1 is lower alkyl, lower alkenyl, lower alkynyl, phenyl, substituted phenyl, phenyl-lower alkelene, or substituted phenyl-lower alkylene; PA1 R.sub.2 and R.sub.3 are independently selected from hydrogen, lower alkyl and trifluoromethyl; PA1 R.sub.4 is hydrogen, ##STR9## R.sub.5 is lower alkyl phenyl, or phenyl-lower alkylene; and n is 0, 1 or 2. PA1 R.sub.1 is hydrogen, lower alkyl or halo substituted lower alkyl; PA1 R.sub.2 is hydrogen, ##STR11## or ##STR12## R.sub.3 is hydrogen, lower alkyl, phenyl or phenyl lower alkyl; Pr-COOR is a substituted or unsubstituted proline of the structure ##STR13## R.sub.4 is hydrogen, lower alkyl, hydroxy, halogen, keto, azido, cycloalkyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, ##STR14## or Y-R.sub.6 ; R.sub.5 is hydrogen or lower alkyl; PA1 Y is oxygen or sulfur; PA1 R.sub.6 is lower alkyl, lower alkenyl, lower alkynyl, phenyl, substituted phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, 1- or 2-naphthyl, substituted 1- or 2-naphthyl, biphenyl, or substituted biphenyl; PA1 R.sub.7 is halogen or -Y-R.sub.8 ; PA1 R.sub.8 is lower alkyl, phenyl, phenyl-lower alkyl, substituted phenyl-lower alkyl, biphenyl, 1- or 2-naphthyl, substituted 1- or 2-naphthyl, substituted biphenyl or the R.sub.8 groups join to complete an unsubstituted 5- or 6-membered ring or such ring wherein a carbon atom is substituted by a lower alkyl or di(lower alkyl) group; PA1 R.sub.9 is keto, phenyl, 2- or 4-hydroxyphenyl; and salts of the formula I compounds. PA1 R.sub.4 is hydrogen, lower alkyl, cyclohexyl, ##STR28## or Y-R.sub.6. R.sub.6 is lower alkyl of 1 to 4 carbons, ##STR29## a substituted or unsubstituted 1- or 2-naphthyl of the formula ##STR30## or a substituted or unsubstituted biphenyl of the formula ##STR31## p is zero, one or two; R.sub.14 is hydrogen, methyl, methoxy, methylthio, Cl, F, Br, or hydroxy; PA1 R.sub.7 is Cl, F, or -Y-R.sub.8 ; PA1 R.sub.8 is lower alkyl of 1 to 4 carbons or the R.sub.8 groups join to complete an unsubstituted 5- or 6-membered ring or said ring in which one or more of the carbons has a methyl or dimethyl substituent; PA1 R.sub.9 is phenyl, 2- or 4-hydroxyphenyl. PA1 R.sub.2 is hydrogen, and R.sub.1 is hydrogen. PA1 R.sub.2 is ##STR32## R.sub.1 is hydrogen, and R.sub.3 is lower alkyl.
Ondetti et al. in U.S. Pat. No. 4,154,935 disclose halogenated compounds which have the general formula ##STR5## wherein R is hydrogen lower alkanoyl or ##STR6## R.sub.1 is hydrogen or lower alkyl; R.sub.2 and R.sub.2 ' each is hydrogen or halogen;
Iwao et al. in U.K. patent application GB 2027025 A disclose compounds of the formula ##STR7## wherein R.sub.1 is phenyl, hydroxyphenyl mercapto-lower alkyl, higher alkyl, higher alkenyl, cycloalkyl, aralkyl, aralkenyl, substituted cycloalkyl, substituted aralkyl, substituted aralkenyl, substituted phenyl, substituted napthyl,
Ondetti et al. in U.K. patent application GB 2028327 A disclose compounds of the formula ##STR8## X-R.sub.1 is located at the 3- or 4- position of the proline ring; X is oxygen or sulfur;